Clinical Trials for Individuals Failing Current Therapy

From San Francisco General Hospital

October 1999

A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

A decade ago, there were only two therapeutic options for people who tested positive for the human immunodeficiency virus: You could take AZT . . . or you could elect not to take AZT. If you chose therapy, you got some benefit -- partial suppression of viral replication, and a modest rebound in your CD4 count -- and these benefits often lasted for several years before they began to wane. If you chose to eschew AZT monotherapy, you were spared the side effects of therapy . . . but you were denied its benefits.

Today, individuals who are beginning antiretroviral therapy have dozens of therapeutic options -- and they have virtual assurance that whatever regimen they choose will suppress viral replication to levels so low they cannot be measured by the most sensitive of the commercially available HIV RNA assays. Moreover, they now have the option of choosing their initial anti-HIV regimen with its successor in mind. Newly diagnosed patients can begin their treatment with a combination of three nucleoside analogs -- AZT, 3TC, and abacavir, for example. Or they can start therapy with two nucleosides and a non-nucleoside reverse-transcriptase inhibitor -- say, d4T, 3TC, and either nevirapine or efavirenz.

In most treatment-naïve individuals, any one of these combinations will suppress viral replication to undetectable levels for a period of time ranging from months to years. And all of these therapeutic choices defer the use of the most powerful class of antiretroviral agents, the protease inhibitors, until a later date -- thereby reserving these potent drugs for use down the road.

But what about the thousands of HIV-positive people who are veterans of two, three, or even four antiretroviral regimens? For these treatment-experienced individuals, who have, over the years, moved from two-nucleoside therapy to an NNRTI-containing regimen, and from there to the first of several multidrug therapies that contained at least one protease inhibitor, the therapeutic options are much more limited. Some of these treatment veterans have developed high-level resistance to several once-effective anti-HIV drugs; others have "burned" whole classes of antiretroviral agents.

The following list -- of clinical trials that are open to individuals who have broken through on their current antiretroviral regimen -- offers a range of options to people who have been on therapy for many years, and who have, as an inevitable consequence, been on many therapies. This is a selective listing; for a complete list of clinical trials that are now enrolling treatment-experienced individuals, call 1-800-TRIALS-A.

In conformance with standard practice, we have listed the drugs that are being tested in these trials by their chemical name. For the brand names of these agents, see the box at the bottom of the page. Agents that are still undergoing clinical testing and have yet to win F.D.A. approval, such as MKC-442 and T-20, do not yet have brand names.

THERAPEUTIC OPTIONS FOR PATIENTS WHO BREAK THROUGH
DESPITE ADHERENCE TO THEIR ASSIGNED COMBINATION THERAPY

Drug(s) Being Tested

Trial Number

Major Inclusion/Exclusion Criteria

ABT-378, efavirenz

AD 378

No pregnant or nursing women
PI experience allowed

Amprenavir, indinavir, nelfinavir, lamivudine, abacavir

PRO 20005

No prior use of abacavir, amprenavir, or any NNRTI
No hepatitis within 6 months
No currently active OIs
At least 12 weeks prior indinavir or nelfinavir, with increasing
viral load

Amprenavir, saquinavir, ritonavir, indinavir, efavirenz,
zidovudine,

ACTG 400

Prior nelfinavir for at least 16 weeks with increasing
viral load
No prior exposure to one of the following combinations: AZT+3TC, lamivudine, stavudine,
didanosine d4T+3TC, d4T+ddI, or AZT+ddI Multiple clinical exclusions
No pregnant or nursing women

MKC-442, didanosine, stavudine, nevirapine, hydroxyurea

ICC 601

No prior use of d4T, ddI, or any NNRTI

Adefovir, abacavir, efavirenz, amprenavir

ICC 605

No prior use of any of the study medications
No prior NNRTI use
Failing PI treatment

Amprenavir, ritonavir, nelfinavir, efavirenz

NIH 991

No prior use of abacavir, amprenavir, or efavirenz
No history of intolerance to ritonavir or nelfinavir
No pregnant or nursing women
Several other clinical criteria

Ages between 6 months and 21 years
No serious infections within 2 weeks
No prior use of ritonavir with nelfinavir
No prior pancreatitis or severe peripheral neuropathy
Viral load > 50,000
No pregnant women

Ages between 3 and 16 years
No pregnant or nursing women
No prior treatment with saquinavir and nelfinavir

lodenosine

NCI 97-C-0119

Ages between 6 months and 18 years
No active or very recent OI
No history of pancreatitis
Multiple other clinical criteria

Notes:
 For
information about where these studies are offered in the United States, call
1-800-TRIALS-A.
 For more detailed information about any of these studies, call 1-800-TRIALS-A.
 The study drugs listed are all of the drugs that will be tested in the trial.
You will not necessarily take all of the drugs listed.
List of abbreviations: PI=protease inhibitor; NNRTI=non-nucleoside reverse-transcriptase inhibitor; OI=opportunistic infection; ARV=antiretroviral
Drug synonyms: AZT=zidovudine=Retrovir; ddI=didanosine=Videx; d4T=stavudine=Zerit;
3TC=lamivudine=Epivir; ddC=dideoxycitidine=Hivid; abacavir=Ziagen; nevirapine=Viramune;
delavirdine=Rescriptor; efavirenz=Sustiva; indinavir=Crixivan; ritonavir=Norvir;
saquinavir=Fortavase; nelfinavir=Viracept; amprenavir=Agenerase

A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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